An important new study from Virginia Lee, John Trojanowski, and their colleagues from the University of Pennsylvania. This new work adds to the growing body of evidence which suggests that certain potent biologic therapeutics, such as IVIG, etanercept, and tacrolimus, may have the potential to effectively intervene in the inflammatory mechanisms involved in the pathogenesis of certain neurodegenerative diseases, such as Alzheimer's. This study offers additional evidence supporting the viability of a potential new approach to the treatment of Alzheimer's Disease utilizing potent, biologic-based anti-inflammatory therapeutics, which merits thorough consideration by the Alzheimer research community.
Title Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model.
Author(s) Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM
Institution The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; The Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Clinical Research Center, Chiba-East National Hospital, Chiba, Chiba 260-9712, Japan.
Source Neuron 2007 Feb 1; 53(3) :337-351.
Abstract Filamentous tau inclusions are hallmarks of Alzheimer's disease (AD) and related tauopathies, but earlier pathologies may herald disease onset. To investigate this, we studied wild-type and P301S mutant human tau transgenic (Tg) mice. Filamentous tau lesions developed in P301S Tg mice at 6 months of age, and progressively accumulated in association with striking neuron loss as well as hippocampal and entorhinal cortical atrophy by 9-12 months of age. Remarkably, hippocampal synapse loss and impaired synaptic function were detected in 3 month old P301S Tg mice before fibrillary tau tangles emerged. Prominent microglial activation also preceded tangle formation. Importantly, immunosuppression of young P301S Tg mice with FK506 attenuated tau pathology and increased lifespan, thereby linking neuroinflammation to early progression of tauopathies. Thus, hippocampal synaptic pathology and microgliosis may be the earliest manifestations of neurodegenerative tauopathies, and abrogation of tau-induced microglial activation could retard progression of these disorders.
Language ENG
Pub Type(s) JOURNAL ARTICLE
PubMed ID 17270732
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